Increased drug resistance of meticillin-resistant Staphylococcus aureus biofilms formed on a mouse dermal chip model.

Increased drug resistance of meticillin-resistant Staphylococcus aureus biofilms formed on a mouse dermal chip model.
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DOI:
10.1099/jmm.0.000461
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发表时间:
2017-04
影响因子:
3
通讯作者:
Hara S
Hara S
中科院分区:
医学3区
文献类型:
--
作者:
Jimi S;Miyazaki M;Takata T;Ohjimi H;Akita S;Hara S

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耐甲氧西林金黄色葡萄球菌(MRSA)生物膜形成在人类是严重的临床问题。以前的体外研究已经进行了生物膜生长仅在无机基板上,因此,我们研究了万古霉素(VCM)的耐药性MRSA生物膜生长在皮肤组织上。我们建立了一种新的组织基质模型,即MRSA生长在小鼠皮肤组织片段(真皮芯片,DCs),并比较其对VCM的耐药能力与MRSA生物膜生长在塑料芯片(PC)。对于一个MRSA分离株,我们发现,尽管PC-BF中的最低杀菌浓度(MBC)增加到6.25 µg ml−1,但对于增殖培养物和在PC上形成的生物膜(PC-BF),VCM MIC是相同的(1.56 µ g ml − 1)。相反,DC上形成的生物膜(DC-BF)的MIC和MBC显著增加(分别为25和50 µg ml−1)。此外,DC-BF的最低生物膜消除浓度(100 µg ml−1)高于PC-BF(25 µg ml−1)。使用六种MRSA菌株,我们发现在PC-BF中,c.f.u.随着VCM浓度的增加,菌落数减少,而在DC-BF中,菌落数大大增加,直至达到MIC,并伴随着形成大菌落、较厚的细菌壁和存在许多有丝分裂细胞。我们的研究结果表明,MRSA的VCM耐药更大的DC-BF。我们的结论是,树突状细胞可以提供一个特定的环境,MRSA,增强细菌生长的细胞毒性VCM浓度下,皮肤伤口感染和抗菌药物的影响的研究可能是有用的。
Meticillin-resistant Staphylococcus aureus (MRSA) biofilm formation in humans is of serious clinical concern. Previous in vitro studies have been performed with biofilms grown only on inorganic substrates; therefore, we investigated the vancomycin (VCM) resistance of MRSA biofilms grown on skin tissue. We established a novel tissue substrate model, namely MRSA grown on segments of mouse skin tissue (dermal chips, DCs), and compared its resistance capacity against VCM with that of MRSA biofilms grown on plastic chips (PCs). For one MRSA isolate, we found that the VCM MIC was identical (1.56 µg ml−1) for planktonic cultures and for biofilms-formed on PCs (PC-BF), although the minimum bactericidal concentration (MBC) increased to 6.25 µg ml−1 in PC-BF. On the contrary, the MIC and MBC for biofilms formed on DCs (DC-BF) significantly increased (25 and 50 µg ml−1, respectively). Furthermore, the minimum biofilm-eradicating concentration was higher for DC-BF (100 µg ml−1) than for PC-BF (25 µg ml−1). Using six MRSA strains, we found that in PC-BF, the c.f.u. number decreased with increasing VCM concentration, whereas in DC-BF, it greatly increased until the MIC was reached, accompanied by the formation of large colonies, thicker bacterial walls and the presence of many mitotic cells. Our results indicate that the VCM resistance of MRSA was greater in DC-BF. We conclude that DCs may provide a specific environment for MRSA that enhances bacterial growth under cytotoxic VCM concentrations, and might be useful for the study of skin wound infections and the effects of antimicrobial drugs.
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